Association of VISTA and BTLA polymorphisms with the risk of non-HBV and non-HCV related hepatocellular carcinoma in Western Guangxi, China: a pilot case-control study

Immune checkpoint including VISTA (V-domain Ig suppressor of T cell activation) and BTLA (B and T lymphocyte attenuator) critically regulate tumor immune evasion, and their genetic polymorphisms correlate multiple malignancies. With HBV vaccination and antiviral therapy advancing, non-B non-C hepatocellular carcinoma (NBNC-HCC) prevalence rises, while reliable early diagnosis biomarkers for NBNC-HCC remain lacking. Thus, the present study investigates the associations between VISTA and BTLA polymorphisms and the risk of NBNC-HCC in western Guangxi, China, so as to facilitate targeted high-risk population screening for NBNC-HCC. A total of 125 NBNC-HCC patients and 150 healthy individuals were enrolled. Genotyping of VISTA (rs748113, rs10762477, rs3747862) and BTLA (rs3112270, rs1982809, rs1844089) was performed using multiplex PCR combined with targeted sequencing. The AG vs AA, AG-GG vs AA, and allele G vs A of VISTA rs3747862, as well as the AA vs GG, GA-AA vs GG, AA vs GA-GG, and allele A vs G of BTLA rs1844089, were all associated with a significantly increased risk of NBNC-HCC (p < 0.05). Given the relatively limited sample size and low statistical power, the observed associations between VISTA and BTLA polymorphisms and the risk of NBNC-HCC should be considered hypothesis-generating and require further systematic validation.